Primary Epilepsy Research Articles

The Off-Label Use of Oxcarbazepine In Indonesia

Oxcarbazepine is a second-generation anticonvulsant drug that is a keto analog of carbamazepine. Oxcarbazepine was approved by The National Agency of Drug and Food Control Indonesia (NA-DFC) for generalized epilepsy, tonic-clonic primary and partial epilepsy with or without secondary generalization. However, as other anticonvulsants, oxcarbazepine is also often used without approved indication (off-label). The aim of this study is to investigate the off-label use of oxcarbazepine through an observational study with retrospective data collection. Data were obtained from four hospitals in Yogyakarta, namely Dr. Sardjito Hospital, UGM Hospital, PKU Muhammadiyah Hospital and Bethesda Hospital. Off-label use of oxcarbazepine was identified based on official registration by NA-DFC Indonesia. The results of this study showed that the use of oxcarbazepine in 2014 was 224 prescriptions, which 117 (52.68%) was off-label. Most off-label indications according to ICD-10 were cephalgia 48 (41.03%), followed by trigeminal neuralgia 35 (29.91%), stroke 6 (5.13%) and others 29 (23.93%). From these study, the off-label use of oxcarbazepine was mostly in the cases of neuropathic pain.

Patterns of Clinical Use of Stereotactic Laser Ablation: Analysis of a Multicenter Prospective Registry

Stereotactic laser ablation (SLA), also termed laser interstitial thermal therapy, is a minimally invasive procedure that is increasingly used in neurosurgery. We wished to examine how and whether SLA is changing the landscape of treatment options for neurosurgical patients. Patients undergoing stereotactic laser ablation were prospectively enrolled in the Laser Ablation of Abnormal Neurological Tissue (LAANTERN) registry. Data from the first 100 enrolled patients are presented here. Clinical indications for SLA include treatment of primary intracranial tumors (48%; 81% being high-grade gliomas [HGGs]), brain metastases (BMs, 34%), epilepsy (16%), and other (2%). For HGGs, SLA was equally likely used for newly diagnosed (45%) or previously treated/recurrent lesions (55%, P= 0.54). By contrast, SLA was predominantly used as treatment for BMs in which radiation therapy/radiosurgery had failed (91%), with only 9% of SLAs performed as initial treatment for newly diagnosed lesions (P < 0.001). Of all SLAs performed, 45% of the procedures were in lieu of surgical resection, with 43% performed because the lesion was not accessible by conventional neurosurgical techniques. HGGs and BMs are the leading indications for SLA in the LAANTERN study. For HGGs, SLA is equally used in the presenting or previously treated/recurrent setting. For BMs, SLA is typically used in the recurrent setting. SLAs are equally likely to be performed for difficult-to-access lesions or in lieu of conventional open surgery.

Trends in epilepsy admissions in children, 1981–2013: population-based observational study using the Scottish national hospital discharge database

ObjectiveTo examine trends in epilepsy admissions in children from 1981 to 2013.DesignRepeated cross-sectional, population-based study.SettingScotland.PatientsWe identified admissions among children between 1981 and 2013 inclusive. Epilepsy admissions were identified from the...

The primary prevention of epilepsy: A report of the Prevention Task Force of the International League Against Epilepsy.

Among the causes of epilepsy are several that are currently preventable. In this review, we summarize the public health burden of epilepsy arising from such causes and suggest priorities for primary epilepsy prevention. We conducted a systematic review of published epidemiologic studies of epilepsy of 4 preventable etiologic categories-perinatal insults, traumatic brain injury (TBI), central nervous system (CNS) infection, and stroke. Applying consistent criteria, we assessed the quality of each study and extracted data on measures of risk from those with adequate quality ratings, summarizing findings across studies as medians and interquartile ranges. Among higher-quality population-based studies, the median prevalence of active epilepsy across all ages was 11.1 per 1000 population in lower- and middle-income countries (LMIC) and 7.0 per 1000 in high-income countries (HIC). Perinatal brain insults were the largest attributable fraction of preventable etiologies in children, with median estimated fractions of 17% in LMIC and 15% in HIC. Stroke was the most common preventable etiology among older adults with epilepsy, both in LMIC and in HIC, accounting for half or more of all new onset cases. TBI was the attributed cause in nearly 5% of epilepsy cases in HIC and LMIC. CNS infections were a more common attributed cause in LMIC, accounting for about 5% of all epilepsy cases. Among some rural LMIC communities, the median proportion of epilepsy cases attributable to endemic neurocysticercosis was 34%. A large proportion of the overall public health burden of epilepsy is attributable to preventable causes. The attributable fraction for perinatal causes, infections, TBI, and stroke in sum reaches nearly 25% in both LMIC and HIC. Public health interventions addressing maternal and child health care, immunizations, public sanitation, brain injury prevention, and stroke prevention have the potential to significantly reduce the burden of epilepsy.

Risk of Unnatural Mortality in People With Epilepsy

People with epilepsy are at increased risk of mortality, but, to date, the cause-specific risks of all unnatural causes have not been reported. To estimate cause-specific unnatural mortality risks in people with epilepsy and to identify the medication types involved in poisoning deaths. This population-based cohort study used 2 electronic primary care data sets linked to hospitalization and mortality records, the Clinical Practice Research Datalink (CPRD) in England (from January 1, 1998, to March 31, 2014) and the Secure Anonymised Information Linkage (SAIL) Databank in Wales (from January 1, 2001, to December 31, 2014). Each person with epilepsy was matched on age (within 2 years), sex, and general practice with up to 20 individuals without epilepsy. Unnatural mortality was determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes V01 through Y98 in the Office for National Statistics mortality records. Hazard ratios (HRs) were estimated in each data set using a stratified Cox proportional hazards model, and meta-analyses were conducted using DerSimonian and Laird random-effects models. The analysis was performed from January 5, 2016, to November 16, 2017. People with epilepsy were identified using primary care epilepsy diagnoses and associated antiepileptic drug prescriptions. Hazard ratios (HRs) for unnatural mortality and the frequency of each involved medication type estimated as a percentage of all medication poisoning deaths. In total, 44 678 individuals in the CPRD and 14 051 individuals in the SAIL Databank were identified in the prevalent epilepsy cohorts, and 891 429 (CPRD) and 279 365 (SAIL) individuals were identified in the comparison cohorts. In both data sets, 51% of the epilepsy and comparison cohorts were male, and the median age at entry was 40 years (interquartile range, 25-60 years) in the CPRD cohorts and 43 years (interquartile range, 24-64 years) in the SAIL cohorts. People with epilepsy were significantly more likely to die of any unnatural cause (HR, 2.77; 95% CI, 2.43-3.16), unintentional injury or poisoning (HR, 2.97; 95% CI, 2.54-3.48) or suicide (HR, 2.15; 95% CI, 1.51-3.07) than people in the comparison cohort. Particularly large risk increases were observed in the epilepsy cohorts for unintentional medication poisoning (HR, 4.99; 95% CI, 3.22-7.74) and intentional self-poisoning with medication (HR, 3.55; 95% CI, 1.01-12.53). Opioids (56.5% [95% CI, 43.3%-69.0%]) and psychotropic medication (32.3% [95% CI, 20.9%-45.3%)] were more commonly involved than antiepileptic drugs (9.7% [95% CI, 3.6%-19.9%]) in poisoning deaths in people with epilepsy. Compared with people without epilepsy, people with epilepsy are at increased risk of unnatural death and thus should be adequately advised about unintentional injury prevention and monitored for suicidal ideation, thoughts, and behaviors. The suitability and toxicity of concomitant medication should be considered when prescribing for comorbid conditions.

Analysis of the Expression of Angioarchitecture-related Factors in Patients with Cerebral Arteriovenous Malformation.

Background:Cerebral arteriovenous malformation (cAVM) is a type of vascular malformation associated with vascular remodeling, hemodynamic imbalance, and inflammation. We detected four angioarchitecture-related cytokines to make a better understanding of the potential aberrant signaling in the pathogenesis of cAVM and found useful proteins in predicting the risk of cerebral hemorrhage.Methods:Immunohistochemical analysis was conducted on specimens from twenty patients with cAVM diagnosed via magnetic resonance imaging and digital subtraction angiography and twenty primary epilepsy controls using antibodies against vascular endothelial growth factor receptor-2 (VEGFR-2), matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule (VCAM-1), and endothelial nitric oxide synthase (eNOS). Western blotting and real-time fluorescent quantitative polymerase chain reaction (PCR) were performed to determine protein and mRNA expression levels. Student's t-test was used for statistical analysis.Results:VEGFR-2, MMP-9, VCAM-1, and eNOS expression levels increased in patients with cAVM compared with those in normal cerebral vascular tissue, as determined by immunohistochemical analysis. In addition, Western blotting and real-time PCR showed that the protein and mRNA expression levels of VEGFR-2, MMP-9, VCAM-1, and eNOS were higher in the cAVM group than in the control group, all the differences mentioned were statistically significant (P < 0.05).Conclusions:VEGFR-2, MMP-9, VCAM-1, and eNOS are upregulated in patients with cAVM and might play important roles in angiogenesis, vascular remodeling, and migration in patients with cAVM. MMP-9, VEGFR-2, VCAM-1, and eNOS might be potential excellent group proteins in predicting the risk of cerebral hemorrhage at arteriovenous malformation.

9 Retrospective survey of epilepsy and anticonvulsant usage in patients with acquired brain injury (abi) at a national rehabilitation hospital

Objective There is a lack of data with regard to the epidemiology of epilepsy in patients admitted to the NRH. Developing the knowledge base is likely to help inform prescribing practice, risk discussion, education of patients and staff thereby improve care and clarity of communication both to people with epilepsy and those involved in supporting them. This study aimed to gather data on: 1. Epidemiology of seizures/epilepsy relating to in-patients at the 2. NRH, Anticonvulsant prescribing practice Method A proforma was developed identifying key factors pertaining to epilepsy/seizures. This was piloted on 5 cases and amendments made. Discharge letters of all patients with ABI, discharged between 1/1/14–31/12/14 were analysed retrospectively using this proforma and data extracted. Results A total of 279 discharge letters were examined (181M, 98F). 52 patients had a diagnosis of epilepsy at the time of admission. 42 patients (36M, 16F) had a diagnosis of secondary epilepsy and 10 a diagnosis of primary epilepsy. Of the 42 cases, 23 had had neurosurgical intervention post brain injury. Secondary epilepsy occurred with greater frequency in patients with traumatic brain injury (n=20), haemorrhagic stroke n=7), brain space occupying lesion (n=7) as compared to ischaemic stroke patients (n=3). 43%% (n=120) individuals were on anticonvulsants at admission for diverse reasons, mostly seizures 15.8% (n=44) and neuropathic pain 10% (n=28). In 33 patients out of 120, no clear indication was evident for their anticonvulsant prescription. Most frequently prescribed anticonvulsants were levetiracetam 21% (58), pregabalin 7.52% (21), sodium valproate 4.65% (13), and gabapentin 2.86% (8). Eleven patients had seizures during admission and in three, seizures occurred during weaning of anti-convulsants. Seizure rescue medication i.e. buccal midazolam was prescribed for 7 of 279 on discharge. Conclusion Secondary epilepsy is common in this population examined. It was more prevalent in those who underwent neurosurgical intervention. Seizures and neuropathic pain were main reasons to be on anticonvulsants. Levetiracetam was the most commonly prescribed agent. Weaknesses of the study were the retrospective study design, the poverty of detail on seizure type, reasons for prescription of anticonvulsants and reliance on accuracy of discharge letters. Qualitative work is needed to look at experience of epilepsy in this group with long term follow up to help inform education, discussions and treatment.

A review of people who did not attend an epilepsy clinic and their clinical outcomes

PurposeTo review the clinical outcomes of people who failed to attend or failed subsequent follow up in a Primary Care based specialist epilepsy service. MethodThe case notes of 200 people who had failed to initially attend the service or subsequent follow up from 2005 to 2013 were reviewed. ResultsClinical outcomes were determined for 152 people, with the remaining 48 having left the area. For those not attending at all, 64% had no further recorded events, a further 22% came under alternative specialist care and were managed appropriately, 6% were already in remission at the time of referral or at follow up and stayed seizure free. For people attending, but were subsequently lost to follow up, 78% were in remission, had improved seizure frequency, and normal pregnancies. In total 6% of those with poor control came under subsequent Neurological care. ConclusionThis study suggests that for the majority of people who fail to attend or are lost to follow up in a primary care specialist epilepsy clinic, the primary reasons appear to be that they had no further events, improved seizure control or that seizure remission has been achieved. The majority with persistent poor control came under Neurological care.

Sleep problems in pediatric epilepsy and ADHD: The impact of comorbidity.

Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in pediatric epilepsy. Although sleep problems are commonly reported in both children with primary ADHD and epilepsy, those with epilepsy-ADHD comorbidity have not been well studied. This study aimed to compare sleep problems among three groups of children: 1) children with epilepsy, 2) children with epilepsy and ADHD (epilepsy-ADHD), and 3) children with primary ADHD. 53 children with epilepsy, 35 children with epilepsy-ADHD, and 52 children with primary ADHD completed the Children's Sleep Habits Questionnaire (CSHQ). Neurology clinic charts were reviewed for the epilepsy-related variables. ADHD subtypes were diagnosed according to the DSM-IV. Children with epilepsy-ADHD had the highest CSHQ total scores, while children with primary ADHD had higher scores than those with epilepsy. Besides the total score, epilepsy-ADHD group differed from the primary ADHD and epilepsy groups with higher CSHQ subscores on sleep onset delay and sleep anxiety. The frequency of moderate-severe sleep problems (CSHQ>56) was 62.9% in children with epilepsy-ADHD, while it was 40.4% and 26.4% in children with primary ADHD and epilepsy, respectively. CSHQ total scores were not different between ADHD subtypes in both children with epilepsy-ADHD and those with primary ADHD. None of the epilepsy-related variables were found to be associated with CSHQ scores. Epilepsy-ADHD is associated with a significantly poor sleep quality which is beyond that of primary ADHD and epilepsy.

Epilepsy awareness and emergency rescue training: Ignorance is bliss!

Status epilepticus (SE) has a high mortality rate and is associated with complications such as neurological deficit and cognitive decline. Buccal midazolam is the recommended emergency rescue medication in the UK to reduce the duration of a seizure and SE. It should be administered by an appropriately trained person. There are agreed guidelines on training standards for its administration in the UK produced by the Joint Epilepsy Council of the United Kingdom and Ireland. Training should provide an overview of epilepsy to facilitate safe, person-centered care and appropriate administration of rescue medication to people with epilepsy (PWE). Unfortunately the current guidelines do not assure satisfactory practice. An investigation was conducted to quantify the nature and degree of the problem in Cornwall, UK (population 550,000). To address the identified inconsistencies, a web-based test was developed using a focus group of experts and stakeholders. Over 800 carers for PWE took the test at different intervals of its development. A consistent 20% failure rate was noted. Over 90% of participants felt it kept PWE safer. The test was incorporated into routine clinical practice and has contributed to reduction of primary epilepsy deaths. The e-test is a cost-effective solution to help harmonize practices across different settings and can be easily adopted by other countries.

Increased NRG1-ErbB4 signaling in human symptomatic epilepsy

Previous studies have shown that the neuregulin 1 (NRG1)-ErbB4 signaling pathway may regulate the excitability of fast-spiking neurons in the frontal cortex and participate in primary epilepsy pathogenesis. However, the exact roles and mechanism for NRG1/ErbB4 in human symptomatic epilepsy are still unclear. Using fresh human symptomatic epilepsy tissues, we found that the protein levels of NRG1 and ErbB4 were significantly increased in the temporal cortex. In addition, NRG1-ErbB4 signaling suppressed phosphorylation of GluN2B at position 1472 by Src kinase, and decreased levels of phosphorylation level of GluN2B and Src were detected in human symptomatic epilepsy tissues. Our study revealed a critical role of the NRG1-ErbB4 signaling pathway in symptomatic epilepsy, which is different from that in primary epilepsy, and we propose that the NRG1-ErbB4 signaling may act as a homeostasis modulator that protects the brain from aggravation of epileptiform activity.

Comorbidities of epilepsy.

In epilepsy management, control of seizures is the prime objective. However, the quality of life is affected by comorbid conditions that include the neurological, neuropsychiatric, and neurobehavioural disorders. These are not only reactive processes to a chronic condition but also have a bidirectional relationship, sharing common underlying pathogenesis. This article besides addressing these issues also explores the therapeutic management. A systematic search of PubMed from Jan 2006 to August 2016 was undertaken using the terms "comorbidities" and "epilepsy." In addition, articles specifically from India and other original papers were selected based on relevance. In this review, the neuropsychiatric, neurobehavioral (mood disorders, behaviour issues, attention deficits, psychosis), and neurologic [cognitive impairment, migraine, SUDEP-Sudden unexpected death in epilepsy (SUDEP)] comorbidities are covered in relation to epilepsy and its treatment. The incidental disorders such as hypertension, diabetes, and cancer that are mentioned in some reports have not been addressed here. Comorbidities in epilepsy are common but poorly understood and often remain unaddressed. The prevalence of comorbid conditions is considerably higher in epilepsy than seen in the general population and other chronic conditions. There is a wide spectrum of secondary disorders that have a marked impact and significantly increase the burden of the primary epilepsy condition. There is a need to acknowledge, screen, and intervene early in newly diagnosed cases for the optimal management of epilepsy.

Review: Roles for astrocytes in epilepsy: insights from malformations of cortical development.

Malformations of cortical development (MCDs), such as cortical dysplasia and tuberous sclerosis complex, are common causes of intractable epilepsy, especially in paediatric patients. Recently, mounting evidence points to a common pathology of these disorders. Hyperactivation of mammalian target of rapamycin (mTOR) has been proposed as a central mechanism in most, if not all, MCDs. The transition from mTOR hyperactivation and cellular abnormalities to large-scale functional changes and seizure is, however, not fully understood. In this article we set out to review currently available information regarding MCD pathology, focusing on glial cells - especially astrocytes - and their interactions with the brain vascular system. A large body of evidence points to these elements as potential targets in MCD. Here, we attempt to provide a review of this evidence and propose some hypotheses regarding the possible chain of events linking primary glial dysfunction and epilepsy. We focus on extracellular matrix remodelling, blood-brain barrier leakage and failure of astrocyte-dependent removal of extracellular debris. We posit that the failure of these systems results in a chronically pro-inflammatory environment, maintaining local astrocytes in a state of gliosis, with increased susceptibility to seizures as a consequence.

A Bio-Electrical Tornado in The Hippocampus: Mechanisms of Temporal Lobe Epilepsy

This review summarizes the structural and electrophysiological changes in the epileptic hippocampus in various animal models of epilepsy. Tornado hypothesis of epileptic hippocampus, states that there are many progressive detrimental changes in the hippocampus of the epileptic rats. PTZ, PTZ kindling, pilocarpine, electrical kindling, kainic acid, hyperthermia and in vitro models are taken as primary animal epilepsy models in this review. Paired pulse inhibition and GABAergic transmission is decreased in dentate gyrus (DG), CA3 and CA1 regions of the epileptic hippocampus. There is interneuron loss in the hilus, DG and CA3, while excitatory input from perforant path (PP) is increased and this is fed into the CA3 area by mossy fibers (MF) which have excessive sprouting that forms novel recurrent synapses with the pyramidal cells of CA3. Gate function of DG is either impaired or lost. CA3 area of hippocampus becomes an epileptic focus and sends ictal discharges. These ictal discharges are carried into CA1 by Schaffer collaterals and then into entorhinal cortex (EC). The input from EC is amplified in the hippocampal circuitry which is fed into hippocampus from EC into DG again successively. Thus a weak electrical input into the hippocampal formation results in an amplified signal back into EC. Since the basic ultrastructural and electrophysiological feed-back control mechanisms are impaired, this electrical tornado cannot be compensated for and an epileptic amplified ictal discharge spreads to the limbic system and other adjacent structures of the brain. Eventually the hippocampal circuitry, that has developed a vicious circle, becomes a bio-electrical amplifier which triggers an electrical tornado, under certain bio-chemical conditions.

Correlation between secondary thrombosis in epileptic patients and serum levels of folate and vitamin B12.

Epilepsy is a chronic brain dysfunction syndrome and nervous system disease whose pathogenesis remains to be determined. The aim of the present study was to analyze the correlation between secondary thrombosis and the serum levels of folate and vitamin B12 in epileptic patients, as well as to determine whether the supplementation of folate and vitamin B12 was associated with a decreased incidence of thrombosis, and provide the basis for novel clinical treatment. A total of 37 patients, diagnosed as epileptic with secondary thrombosis between April 2012 and April 2014, were included in the treatment group. A total of 37 epileptic patients without secondary thrombosis were included in the control group. The serum levels of homocysteine, folate and vitamin B12 in the two groups and in the epileptic patients with intracranial thrombosis or peripheral thrombosis were compared. According to the Guidance of Epilepsy, the patients in the two groups were administered antiepileptic drugs (AEDs) with the supplementation of folate tablet (0.4 mg/day) and vitamin B12 tablet (100 µg/day). These indicators and the incidence of thrombosis in the two groups were compared after 1 year. The serum levels of homocysteine in the two groups were higher than normal, and the levels in the treatment group were significantly higher than those in the control group. The serum levels of folate and vitamin B12 in the treatment group were significantly higher than those in the control group and the difference was statistically significant (P<0.05). The Pearson correlation analysis revealed that the serum levels of folate and vitamin B12 were not associated with the serum level of homocysteine (P>0.05). The logistic regression analysis revealed that the serum levels of folate and vitamin B12 were independent risk factors for epilepsy with secondary thrombosis [folate: odds ratio (OR)=0.635, P=0.038; vitamin B12: OR=0.418, P=0.042]. The differences in the serum levels of homocysteine, folate and vitamin B12 in the epileptic patients with intracranial thrombosis or peripheral thrombosis were not statistically significant (P>0.05). The serum levels of homocysteine in the two groups, were significantly decreased, while the levels of folate and vitamin B12 were significantly increased. The differences in the serum levels of homocysteine, folate and vitamin B12 in the two groups were not statistically significant (P>0.05). The differences in the incidence of thrombosis in the two groups were not statistically significant (P>0.05). In conclusion, the serum levels of folate and vitamin B12 were independent of serum homocysteine, and were the dependent risk factors for primary epilepsy with secondary thrombosis. The supplementation of folate and vitamin B12 may be beneficial for the prevention of epilepsy with secondary thrombosis, making it valuable in application.

Determining the disability adjusted life years lost to childhood and adolescence epilepsy in southeast Nigeria: An exploratory study

ObjectivesDisease burden has always been based on associated mortality. An accurate measurement of the burden of epilepsy should rely on both morbidity and mortality. This will close any existing gap in knowledge and provide useful information to aid evidence-based decision-making. In this study, burden of epilepsy was estimated, using disability-adjusted-life-years (DALYs), using disability weights for epilepsy that were part of the Global Burden of Disease 2010 work. MethodsThe study was conducted at the University of Nigeria Teaching Hospital, Enugu. Interviewer-administered questionnaire was used to collect information from patients with epilepsy who presented to neurology clinic. The prevalence of epilepsy, and case-fatality were obtained from previous publications. The DALYs were estimated by adding together the years lost to disability (YLDs) and years lost to life (YLLs) to epilepsy (DALYs=YLD+YLL). DALYs were dis-aggregated by age group and by whether or not epilepsy was treated. ResultsA total of 134 children with epilepsy-interviews were conducted. Some 56% and 44% of the subjects had primary and secondary epilepsy, respectively. The childhood epilepsy caused 1.63 YLLs per 1000 population, 0.45 YLDs per 1000 population and 2.08 DALY per 1000 population. The highest burden was in children within the age group of 5–14 years at 2.18 DALY per 1000 people. The YLDs was higher (0.63/1000 population) among the untreated group, compared with the YLDs (0.27/1000 population) among the treated group. The YLLs lost for children with secondary epilepsy (2.23/1000 population) was higher than primary epilepsy YLLs of 1.07/1000 population. SignificanceThe DALYs due to childhood epilepsy was high. The YLDs was high among children with epilepsy who were not on treatment. The YLLs were found to be the same in all children with epilepsy, irrespective of their treatment status. This imperatively necessitates the de-emphasis on just mortality as an indicator of the burden of childhood epilepsy but rather a holistic approach should be adopted in considering both the mortality and disability in monitoring the outcome of health interventions.

The relationship between valproate induced tremors and circulating neurotransmitters: a preliminary study

Patients with epilepsy and on valproate (VPA) therapy may develop tremors as a common adverse effect; however, its exact mechanisms are unknown. We hypothesize that VPA-induced tremors may be related to the disturbances in dopamine (DA) and catecholamines (norepinephrine (NE) and epinephrine (E)) concentrations (which are also involved in VPA anticonvulsant effect). We aimed to determine the frequency and type of VPA-induced tremors and their risk factors and to investigate whether or not they are related to the plasma DA, NE and E concentrations. This study included 75 adults with primary epilepsy (mean age: 31.90 ± 5.62 years) and on VPA therapy for 10.57 ± 3.55 years and 40 matched healthy controls. Patients were divided according to the absence or presence of tremors. Blood samples were analyzed for DA, NE and E. Intermittent action tremors in both hands were reported in 31 (41.33%). Chronic standard VPA therapy, older age, longer treatment duration and higher serum concentrations of VPA are risk factors for tremors. None of the patients on controlled release VPA had tremors. Compared to controls, patients (without and with tremors) had lower DA (p = 0.0001) and NE (p = 0.01) concentrations. Compared to patients without tremors, patients with tremors had lower levels DA (p = 0.045) and NE (p = 0.01). Significant correlations were identified between DA with NE (r = 0.540, p = 0.001) concentrations and serum VPA with DA (r = −0.285, p = 0.045) and NE (r = −0.358, p = 0.01) plasma levels. We conclude that benign action tremors are common with standard VPA. Mechanisms underlying VPA-induced tremors may involve abnormalities of DA and NE neurotransmitters.

Recruitment of the left precentral gyrus in reading epilepsy: A multimodal neuroimaging study.

PurposeIn a previous study, we investigated a 42-year-old male patient with primary reading epilepsy using continuous video-electroencephalography (EEG). Reading tasks induced left parasagittal spikes with a higher spike frequency when the phonological reading pathway was recruited compared to the lexical one. Here, we seek to localize the epileptogenic focus in the same patient as a function of reading pathway using multimodal neuroimaging.Methods and resultsThe participant read irregular words and nonwords presented in a block-design paradigm during magnetoencephalography (MEG), functional near-infrared spectroscopy (fNIRS), and functional magnetic resonance imaging (fMRI) recordings, all combined with EEG. Spike analyses from MEG, fNIRS, and fMRI–EEGs data revealed an epileptic focus in the left precentral gyrus, and spike localization did not differ in lexical and phonological reading.ConclusionThis study is the first to investigate ictogenesis in reading epilepsy during both lexical and phonological reading while using three different multimodal neuroimaging techniques. The somatosensory and motor control functions of the left precentral gyrus that are congruently involved in lexical as well as phonological reading can explain the identical spike localization in both reading pathways. The concurrence between our findings in this study and those from our previous one supports the role of the left precentral gyrus in phonological output computation as well as seizure activity in a case of reading epilepsy.

The epidemiology of epilepsy in children in the Republic of Belarus

To study the incidence of epilepsy in children in the Republic of Belarus based on the data of the Republican Centre for disease control. Statistical analysis of the incidence and morbidity of epilepsy in children and adolescents was performed. Based on this analysis, the contribution of epilepsy in the neurologic morbidity in childhood was analyzed. The morbidity and incidence of epilepsy in children averaged 0.35 and 2.4 per 1000 of the child population, respectively, over the last 6 years (2009-2014). The peak incidence of primary epilepsy is between the ages 1-4 years (0.43 per 1000 population for 12 years (2003-2014), of incidence of epilepsy among children, aged 0-17 years, are stable with no significant fluctuations for the last 6 years (2009-2014). The proportion of epilepsy in the structure of neurological disorders (9.51%) remained unchanged. In the period 2003-2014, general incidence of epilepsy among children, aged 5-9 years, has increased from 2.2 to 2.6 per 1000 child population (p<0.05) and from 2.5 to 3.8 (p<0.05) in children, aged 15-18 years, with no changes in the morbidity.

Safety of Overnight Switch from Brand-Name to Generic Levetiracetam.

Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. The objective of this study was to evaluate the safety and tolerability of the brand-to-generic levetiracetam switch in patients with focal or generalized epilepsy. A prospective study in patients with primary, cryptogenic or symptomatic epilepsy, who were taking branded levetiracetam and were switched to generic levetiracetam. Patients were consecutively recruited from January 2013 to January 2015. We evaluated efficacy, tolerability and compliance before switching (T0) and after 6 months of therapy (T1). Evaluations were scheduled as follows: baseline, 7 and 15 days, 1, 3 and 6 months. At each visit clinical diary seizures, physical and neurological examination, laboratory parameters and electroencephalogram were evaluated. Fifty-nine patients, equally mixed by sex, were included in the study. Mean age was 26.1 years. Forty-seven per cent of the patients enrolled received levetiracetam as monotherapy. One patient was lost during the follow-up: so at T1 we had 58 patients (28 monotherapy and 30 polytherapy). At T0 and at T1, there was no statistically significant difference in terms of seizure frequency and intensity, occurrence of adverse events, laboratory parameters and electroencephalographic features. Two patients stopped treatment with the generic (both at 3 months after the switch) and restarted therapy with brand levetiracetam because of seizure increase. At the end of the study, the switchback rate was 3.4%. No increase of seizures and adverse effects were observed when branded levetiracetam was interchanged to a generic equivalent. More studies should be conducted with a larger series of patients to confirm these results.